Avelumab (Bavencio, Merck KGaA/Pfizer Inc.) did not improve overall survival compared with docetaxel in a phase 3 trial among patients with unresectable, recurrent, or metastatic non–small-cell lung cancer (NSCLC) whose tumors were positive for programmed death ligand-1 (PD-L1+) and whose disease had progressed after treatment with a platinum-containing doublet therapy.
The JAVELIN Lung 200 trial did not meet its prespecified endpoint of improving overall survival (OS) among patients whose tumors were PD-L1+ by 1% or more, the companies announced. The hazard ratio (HR) was 0.90 (96% confidence interval [CI], 0.72–1.12; one-sided P = 0.1627).
However, the proportion of patients in the chemotherapy arm crossing over to immune checkpoint inhibitors outside the study was higher than previously reported in post-platinum immunotherapy clinical trials, the companies said, and this may have confounded the trial outcome. The percentage of patients receiving subsequent checkpoint inhibitor therapy was 26.4% in the docetaxel arm and 5.7% in the avelumab arm.
Improvements in OS versus the control arm were observed in the moderate-to-high PD-L1+ expression (50% or greater, which represented approximately 40% of the study population) and high PD-L1+ expression population (PD-L1+ expression 80% or greater, which represented approximately 30% of the study population) (HR, 0.67; 95% CI, 0.51–0.89; two-sided P = 0.0052, and HR, 0.59; 95% CI, 0.42–0.83, two-sided P = 0.0022, respectively). The safety profile for avelumab was consistent with that observed in the overall JAVELIN clinical development program.
"Avelumab performed in line with expectations in the trial from both an efficacy and safety perspective," said primary investigator Fabrice Barlesi, MD, PhD, Head of Multidisciplinary Oncology and Therapeutic Innovations Department at Aix-Marseille University and the Assistance Publique Hôpitaux de Marseille, France. "With immune checkpoint inhibitors approved for patients with previously treated, advanced non–small-cell lung cancer, higher percentages of immunotherapy-naïve patients are receiving subsequent checkpoint inhibitors in their progressive treatments. This was observed in the JAVELIN Lung 200 control arm and may have confounded the primary outcome of the study."
"We are committed to understanding the data in the context of the subpopulations and the impact of access to other immune checkpoint inhibitors," said Chris Boshoff, MD, PhD, Senior Vice President and Head of Immuno-Oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "We will continue to progress the broad avelumab program, exploring various indications."
Detailed results from the JAVELIN Lung 200 trial will be submitted for presentation at an upcoming medical congress, and the companies aim to share the data with regulatory agencies.
In 2017, avelumab received accelerated approval by the FDA for metastatic Merkel cell carcinoma and for previously treated patients with locally advanced or metastatic urothelial carcinoma.
The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 7,000 patients evaluated across more than 15 different tumor types. JAVELIN Lung 200 is a randomized, open-label, multicenter trial including 792 patients from approximately 260 sites in North America, South America, Asia, Africa, Australia and Europe.
Avelumab is a human anti-PD-L1 antibody that has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T-cell-mediated antitumor immune response. Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.
Source: Merck KGaA; February 15, 2018.